Orientation selectivity and binding enhancement with E6 protein are demonstrated by nano-structured mixed-SAMs systems of different chain lengths. Mixtures of n-alkinethiol SAMs of different chain lengths: 1-Decanethiol (C9) and 1-Hexanethiol (C5) are the examples in present work The demonstrations include the molecular dynamics simulations on the binding energies of a single E6 protein molecule with mixed SAMs molecules and the binding force measurements by Atomic Force Microscope (AFM) for a cluster of E6 protein molecules at different orientations with the same SAMs.